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Mol Pharm. 2009 Nov-Dec;6(6):1662-77. doi: 10.1021/mp800246x.

Impact of hepatic uptake transporters on pharmacokinetics and drug-drug interactions: use of assays and models for decision making in the pharmaceutical industry.

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1
Department of Discovery DMPK, AstraZeneca R&D Charnwood, Bakewell Road, Loughborough, Leicestershire LE115RH, UK.

Abstract

The ability to predict hepatic metabolic clearance is a key component in the design and selection of small molecule drug candidates within the pharmaceutical industry. The recognition that metabolism-transporter interplay can influence hepatic metabolic clearance has presented new challenges, both in terms of the creation of experimental systems suitable for an industry setting and also in developing an understanding of the pharmacokinetic concepts that underpin them. This paper reviews the pharmacokinetic principles that govern the kinetics of uptake transporter substrates. In addition, new data are presented from a range of test systems for assessing hepatic drug clearance and the impact of drug-drug interactions (DDIs).

PMID:
19402709
DOI:
10.1021/mp800246x
[Indexed for MEDLINE]

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